This project is concerned with all aspects of cholesterol metabolism, with special emphasis on control of blood cholesterol concentration and its relation to the rate of progression of atherosclerosis. At an earlier state we identified a number of intermediates in cholesterol biosynthesis, and confirmed some of the structures by organic synthesis. A small amount of work in organic synthesis is still under way. Our main effort is currently directed at the question of transfer of cholesterol between the blood and the tissues. We are studying the movement of cholesterol between the liver and the various lipoproteins, both by chemical analysis to estimate net transfer and by radioisotope techniques. We are also working on the identification of a high molecular weight substance present in the 100,000 X G supernatant of normal rat liver and required for cholesterol synthesis from acetate. This substance disappears after a short period of cholesterol feeding. BIBLIOGRAPHIC REFERENCES: Taddeini, L., Frantz, I.D., Jr., and Sanghvi, A., Acceleration of hepatic sterol synthesis after a single dose of porphyrogenic chemical allylisopropylacetamide. J. Lipid Res. 15:84, 1974. Sanghvi, A., Wight, C., Balachandran, R., Frantz, I.D., Jr., Ener, M., and Taddeini, L., Cholesterol synthesis in rat intestine: Effect of fasting and of porphyrogenic chemical allylisopropylacetamide. Life Sciences 14:1679, 1974.